Actions and toxicity of nonsteroidal anti-inflammatory drugs

Current Opinion in Rheumatology

Volumn 8, Issue 3, 1996, Pages 169-175

  Simon, Lee S ^a  

^a BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MISOPROSTOL; NONSTEROID ANTIINFLAMMATORY AGENT; SALICYLIC ACID; TENIDAP;

DRUG MECHANISM; DRUG USE; GASTROINTESTINAL HEMORRHAGE; HUMAN; OSTEOARTHRITIS; PRIORITY JOURNAL; REVIEW; RHEUMATOID ARTHRITIS;

EID: 0030011357     PISSN: 10408711     EISSN: None     Source Type: Journal    
DOI: 10.1097/00002281-199605000-00001     Document Type: Review

References (48)

1. Brooks PM, Day RO: Nonsteroidal antiinflammatory drugs: differences and similarities. N Engl J Med 1991, 324:1716-1725.
2. Furst DE: Are there differences among nonsteroidal antiinflammatory drugs? Comparing acetylated salicylates, nonacetylated salicylates, and nonacetylated nonsteroidal antiinflammatory drugs. Arthritis Rheum 1994, 37:1-9.
3. Abramson SB, Weissman G: The mechanism of action of nonsteroidal antiinflammatory drugs. Arthritis Rheum 1989, 32:1-9.
4. Bombardier C, Peloso PMJ, Goldsmith CH, Salsalate-Diclofenac Study Group: Salsalate, a nonacetylated salicylate, is as efficacious as diclofenac in patients with rheumatoid arthritis. J Rheumatol 1995, 22:617-624. This is an interesting and well-designed trial demonstrating the utility of nonacetylated salicylates in the treatment of patients with rheumatoid arthritis despite that these drugs are not considered potent inhibitors of inflammation (because in vitro testing demonstrates that these drugs are not potent inhibitors of prostaglandin synthesis).
5. The Multicenter Study Group: Trial of non-acetylated salicylate in RA: does the acetyl group of aspirin contribute to the anti-inflammatory efficacy of salicylic acid in the treatment of rheumatoid arthritis? J Rheumatol 1989, 16:321-327.
6. Fries JF, Spitz PW, Williams CA, et al.: A toxicity index for comparison of side effects among different drugs. Arthritis Rheum 1990, 33:121-130.
7. Singh G, Ramey DR, Morfeld SD, Fries JF: Comparative toxicity of nonsteroidal antiinflammatory agents. Pharmacol Ther 1994, 62:175-191.
8. Singh G, Williams C, Ramey DR, Fries JF: A toxicity index for comparison of the gastrointestinal toxicity of non-steroidal antiinflammatory drugs (NSAID). Arthritis Rheum 1993, 36:B220.
9. Day RO, Quinn DI, Conaghan PG, Tett SE: Adverse drug reactions and their measurement in the rheumatic diseases. J Rheumatol 1995, 22:983-988. These authors present an interesting analysis of an increasingly important area in this age of cost effectiveness.
10. Peloso PM, Wright JG, Bombardier C: A critical appraisal of toxicity indexes in rheumatology. J Rheumatol 1995, 22:989-994. An important overview of the field that evaluates the comparative toxicities of the various NSAIDs.
11. Fries JF: ARAMIS and toxicity measurement. J Rheumatol 1995, 22:995-997. Although flawed, the toxicity measurement system proposed by the group monitoring the ARAMIS database has raised the consciousness of all who treat patients with the various available drugs for arthritis. It is difficult to directly compare potential toxicities produced by disease-modifying drugs and NSAIDs.
12. Meade EA, Smith WL, DeWitt DL: Differential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isozymes by aspirin and other nonsteroidal anti-inflammatory drugs. J Biol Chem 1993, 268:6610-6614.
13. DeWitt DL, Meade EA, Smith WL: PGH synthase isoenzyme selectivity: the potential for safer nonsteroidal antiinflammatory drugs. Am J Med 1993, 95(suppl 2A):40s-44s.
14. DeWitt DL, El-Harith EA, Kraemer SA, et al.: The aspirin and heme-binding sites of ovine and murine prostaglandin synthetases. J Biol Chem 1990, 265:5192-5198.
15. Lee SH, Soyoola E, Chanmugam P, et al.: Selective expression of mitogen-induced cyclooxygenase in macrophages stimulated with lipopolysaccharide. J Biol Chem 1992, 267:25934-25938.
16. O'Banion MK, Winn VD, Young DA: cDNA cloning and functional activity of a glucocorticoid-regulated inflammatory cyclooxygenase. Proc Natl Acad Sci U S A 1992, 89:4888-4892.
17. Mitchell JA, Akarasereenont P, Thiemermann C, Flower RJ, Vane JR: Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase. Proc Natl Acad Sci U S A 1994, 90:11693-11697.
18. Patrignani P, Panara MR, Greco A, Fusco O, Natoli C, Jacobelli S, et al,: Biochemical and pharmacological characterization of the cyclooxygenase activity of human blood prostaglandin endoperoxide synthases. J Pharmacol Exp Ther 1994, 271:1705-1712.
19. Glaser K, Sung M-L, O'Neill K, et al.: Etodolac selectively inhibits human prostaglandin G/H synthase 2 (PGHS-2) versus human PGHS-1. Eur J Pharmacol 1995, 281:107-111. This interesting paper demonstrates the various effects of etodolac on COX-1 and COX-2 activity in different experimental systems. It demonstrates the experimental rationale by which relatively low does of the drug are reasonably well tolerated by the gastrointestinal mucosa yet still provide systemic anti-inflammatory activity. However, as higher doses are achieved, more effects on COX-2 activity are noted.
20. Marcus AJ: Aspirin as prophylaxis against colorectal cancer. N Engl J Med 1995, 333:656-657. An excellent review of an intriguing area regarding novel effects of aspirin.
21. Diaz-Gonzalez F, Gonzalez-Alvero I, Companero MR, et al.: Prevention of in-vitro neutrophil-endothelial attachment through shedding of L-selectin by nonsteroidal antiinflammatory drugs. J Clin Invest 1995, 95:1756-1765. An interesting in vitro observation that if shown in vivo will help explain the effects of the drugs studied.
22. Amin AR, Vyas P, Attur M, et al.: The mode of action of aspirin like drugs: effect of inducible nitric oxide synthetase. Proc Natl Acad Sci U S A 1995, 92:7926-7930. As more information on nitric oxide is accumulated, the effects of NSAIDs on nitric oxide synthetase will be intriguing.
23. Hawkey CJ: Future treatments for arthritis: new NSAIDS, NO NSAIDS, or no NSAIDS [editorial]. Gastroenterology 1995, 109:614-616. This interesting editorial provides a good review of the effects of nitric oxide and presents interesting information about the effects of combination therapy with NSAIDs and nitric oxide on the gastrointestinal tract.
24. Lu X, Xie W, Reed D, et al.: Nonsteroidal antiinflammatory drugs cause apoptosis and induce cyclooxygenases in chicken embryo fibroblasts. Proc Natl Acad Sci U S A 1995, 92:7961-7965. An interesting hypothesis with experimental data as backup.
25. Giovannucci E, Egan KM, Hunter DJ, et al.: Aspirin and the risk of colorectal cancer in women. N Engl J Med 1995, 333:609-614. A well-designed prospective analysis of the incidence of colonic cancers in nurses followed for years who also used aspirin long term. The study suggests that there is reasonable evidence that there is a decreased incidence of colonic carcinoma in patients who use aspirin long term.
26. Pasricha PJ, Bedi A, O'Connor K, et al.: The effects of sulindac on colorectal proliferation and apoptosis in familial adenomatous polyposis. Gastroenterology 1995, 109:994-998. Interesting paper demonstrating that NSAIDs induce apoptosis rather than antiproliferative effects when shrinking the size of polyps in patients with familial adenomatous polyposis.
27. Buring JE, Lee I-M, Hennekens CH: Nonsteroidal antiinflammatory drugs and colorectal cancer. Cancer 1994, 74:1837-1839.
28. Heath CW Jr, Thun MJ, Greenberg EJ, Levin B, Marnett LJ: Nonsteroidal antiinflammatory drugs and human cancer. Cancer 1994, 74:2885-2888.
29. Brandt KD: Toward pharmacologic modification of joint damage in osteoarthritis [editorial]. Ann Intern Med 1995, 122:874-875. An outstanding editorial that reviews the burgeoning field of drug development for patients with osteoarthritis.
30. Otterness IG, Bliven ML, Downs JT, et al.: Inhibition of IL-1 synthesis by tenidap: a new drug for arthritis. Cytokine 1991, 3:277-283.
31. Sipe JD, Bartie LM, Loose LD: Modification of proinflammatory cytokine production by the anti-rheumatic agents tenidap and naproxen: a possible correlate with clinical acute phase response. J Immunol 1992, 148:480-484.
32. Dingle JT, Leeming MRG, Martindale JJ: Effect of tenidap on cartilage integrity in vitro. Ann Rheum Dis 1993, 52:292-299.
33. Pelletier JP, McCollum R, DiBattista J, et al.: Regulation of human chondrocyte IL-1 receptor expression by anti-rheumatic drugs. Arthritis Rheum 1993, 36:1517-1527.
34. Al-Humidan AM, Reilly KM, Leeming MRG, Russell RGR: Tenidap inhibits bone resorption induced by PTH, 1,25 vit D3, IL-1, TNF, and PGE2 in vitro by mechanisms independent of inhibition of prostaglandin synthesis. Arthritis Rheum 1991, 34:S192.
35. Carty TJ, Showell HJ, Loose LD, Kadin SB: Inhibition of both 5-lipoxygenase (5-LO) and cyclooxygenase (CO) pathways of arachidonic acid (AA) metabolism by CP-66.248, a novel antiinflammatory compound. Arthritis Rheum 1988, 31(suppl 4):S89.
36. Madhok R: Tenidap. Lancet 1995, 346:481-485. This is a very important paper for anyone interested in the actions and pharmacology of tenidap.
37. Wylie G, Appelboom T, Bolten W, et al.: A comparative study of tenidap, a cytokine-modulating anti-rheumatic drug, and diclofenac in rheumatoid arthritis: a 24-week analysis. Br J Rheumatol 1995, 34:554-563. A somewhat early analysis of a comparison trial of the effects of tenidap compared with diclofenac in patients with rheumatoid arthritis.
38. Littman BH, Drury CE, Zimmerer RO, et al.: Rheumatoid arthritis treated with tenidap and piroxicam. Arthritis Rheum 1995, 38:29-37. Another comparison trial of tenidap and piroxicam in patients with rheumatoid arthritis. There were no significant differences in clinical parameters between the two drugs. Acute-phase reactants fell more with tenidap than with piroxicam therapy.
39. Evans JMM, McMahon AD, McGilchrist MM, et al.: Topical non-steroidal anti-inflammatory drugs and admission to hospital for upper gastrointestinal bleeding and perforation: a record linkage case-control study. BMJ 1995, 311:22-26. A flawed study that does not prove that topical formulations of NSAIDs are less toxic to the gastrointestinal tract than oral formulations.
40. Silverstein FE, Graham DY, Senior JR, et al.: Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. Ann Intern Med 1995, 123:214-249. This important study, which has its flaws, demonstrates that misoprostol treatment alters outcomes of ulceration, perforation, and obstruction. Hematemesis had a similar incidence in the placebo and misoprostol groups. In the 8843 patients there was only a 1% to 2% incidence of untoward NSAID-induced gastrointestinal events, an incidence somewhat below that expected by the US Food and Drug Administration.
41. Simon LS, Polisson RP, Hatoum HT, Bittman RM: Risk factors for serious NSAID-induced GI complications: the risk-reduction effect of misoprostol therapy in the individual patient [abstract]. Arthritis Rheum 1995, 38(suppl):S322. As yet an abstract related to the Silverstein et al. report (Ann Intern Med 1995, 123:214-249). The investigators demonstrate the risk reduction effects of misoprostol in patients who are at relatively high risk for NSAID-induced gastrointestinal toxicity based on historical and disease factors.
42. Maetzel A, Ferraz M, Bombardier C: A new examination of the cost-effectiveness of misoprostol in preventing serious gastrointestinal bleeding due to NSAIDs [abstract]. Arthritis Rheum 1995, 38(suppl):S323. Also an abstract that deals with the outcomes data reported by Silverstein et al. (Ann Intern Med 1995, 123:214-249). Suggests that there are reasonable pharmacoeconomic data to support the use of misoprostol cotherapy as prophylaxis against NSAID-induced upper gastrointestinal ulceration and its possible serious complications in patients defined to be at high risk.
43. Raskin JB, White RH, Jackson JE, et al.: Misoprostol dosage in the prevention of nonsteroidal anti-inflammatory drug-induced gastric and duodenal ulcers: a comparison of three regimens. Ann Intern Med 1995, 123:344-350. This paper demonstrates that twice daily or even three times daily dosing of misoprostol is useful with only small sacrifice of beneficial effects and significant decreases in toxicity.
44. Larkai EN, Smith JL, Lidsky MD, Graham DY: Gastroduodenal mucosa and dyspeptic symptoms in arthritic patients during chronic nonsteroidal anti-inflammatory drug use. Am J Gastroenterol 1987, 82:1153-1158.
45. Talley NJ, Evans M, Fleming KC, et al.: Nonsteroidal antiinflammatory drugs and dyspepsia in the elderly. Dig Dis Sci 1995, 40:1345-1350. An interesting paper evaluating the incidence of dyspepsia in elderly patients using NSAIDs.
46. 2 antagonists are effective in inhibiting the formation of NSAID-induced gastric ulcers, whereas it is clear that these drugs inhibit the formation of NSAID-induced duodenal ulcers defined by endoscopy.
47. Gebuhr P, Wilbek H, Soelberg M: Naproxen for 8 days can prevent heterotopic ossification after hip arthroplasty. Clin Orthop Rel Res 1995, 314:166-169. A brief paper with clinical data suggesting that naproxen therapy prevents heterotopic ossification after hip arthroplasty. Perhaps this is an antiproliferative effect of the NSAID.
48. Pritchett JW: Ketorolac prophylaxis against heterotopic ossification after hip replacement. Clin Orthop Rel Res 1995, 314:162-165. Another paper describing the effects of a different NSAID on heterotopic ossification in patients with osteoarthritis.